key: cord-0844971-qlxf7ho5 authors: Dilber, Beril; Aydın, Zeynep Gökçe Gayretli; Yeşilbaş, Osman; Sağ, Elif; Aksoy, Nurdan Kaykı; Gündoğmuş, Fırat; Küçükalioğlu, Burcu Parıltan; Yılmaz, Semra Atasoy; Demirhan, Yeşeren Nil; Çelik, Nurşen; Karaca, Abdullah; Ertem, Neşe Yalçın; Özdemir, Ramazan; Aksoy, Halil İbrahim; Öztürk, Emine Esra; Saygın, Berna; Acar, Filiz Aktürk title: Neurological manifestations of paediatric acute COVID infections: A single centre experience date: 2021-07-12 journal: J Trop Pediatr DOI: 10.1093/tropej/fmab062 sha: 79c26dfc1f0e4d3a677d16c5bf57a996b32fb7ab doc_id: 844971 cord_uid: qlxf7ho5 BACKGROUND: Coronavirus disease 2019 (COVID-19) usually leads to a mild infectious disease course in children, while serious complications may occur in conjunction with both acute infection and neurological symptoms, which have been predominantly reported in adults. The neurological complications in these patients vary based on patient age and underlying comorbidities. Data on clinical features, particularly neurological features, and prognostic factors in children and adolescents are limited. The present study provides a concise overview of neurological complications in pediatric COVID-19 cases. MATERIALS AND METHODS: The retrospective study reviewed medical records of all patients who were admitted to our hospital and were diagnosed with COVID-19 by real-time reverse-transcription polymerase-chain-reaction (RT-PCR) assay between March 11, 2020 and January 30, 2021. Patients with a positive PCR result were categorized into two groups: Out Patient Departments (OPD) patients and In Patient Departments (IPD). RESULTS: Of the 2,530 children who underwent RT-PCR during the study period, 382 (8.6%) were confirmed as COVID-19 positive, comprising 188 (49.2%) girls and 194 (50.8%) boys with a mean age of 7.14±5.84 (range, 0-17) years. Neurological complications that required hospitalization were present in 34 (8.9%) patients, including seizure (52.9%), headache (38.2%), dizziness (11.1%) and meningoencephalitis (%5.8). CONCLUSION: The results indicated that neurological manifestations are not rare in children suffering from COVID-19. Seizures, headaches, dizziness, anosmia, ageusia, and meningoencephalitis major neurological manifestations during acute COVID-19 disease. Although seizures were the most common cause of hospitalization in IPD patients, the frequency of meningoensalitis was quite high. Seizures were observed as febrile seizures for children under six years of age and afebrile seizures for those over 6 years of age. Febrile seizure accounted for half of all seizure children. 59 60 Coronavirus disease (COVID-19) is a serious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease spread from a Chinese cluster to almost all other countries within a few weeks in late December 2019. Ever since, the COVID-19 outbreak has drastically changed the world's health concerns and the disease has rapidly spread worldwide, becoming the first pandemic of the 21 st century. As of August 31, 2020, more than 25 million patients have been infected with the disease. (1) . Neurotropic and neuroinvasive capabilities of coronaviruses have been described in humans. Neurological problems found in patients with coronavirus infection include febrile seizures, convulsions, loss of consciousness, encephalomyelitis, and encephalitis. Moreover, neurological manifestations have also been reported in adults with COVID-19 (2) . Despite the high number of people affected, data on clinical features and prognostic factors in children and adolescents are limited (1) (2) (3) . The incidence curves of hospitalized patients increase with age, with most severe cases including adults aged over 80 years. Mortality follows this trend and mainly burdens the elderly, but rarely children (4) (5) . Therefore, children comprise a minority of hospitalized patients (6) . Given the limited number of diagnosed pediatric cases and the low associated morbidity rate in children, the literature on pediatric COVID-19 cases is relatively scarce in comparison with the reports on affected adults. Neurological complications in children have only been reported in a few case reports and reviews . Mao L, Lu X et al. also reported that they did not observe neurological complications in pediatric patients during the acute COVID-19 period (23) (24) . Twenty-one studies/case series and five case reports include in study; non-specific neurological manifestations, presenting altogether in 16.7% cases and 1% were found to have been reported with definite neurological complications (13) , to our knowledge, there has been no single-center study evaluating children and infants with COVID-19 and neurological complications. In our study, neurological complications requiring hospitalization were seen in 8.9%. The present study provides a concise overview of neurological complications in pediatric COVID-19 cases and aimed to investigate neurological complications in pediatric COVID-19 cases admitted to a tertiary care hospital. This retrospective, observational single-center study reviewed medical records of all patients who were admitted to our hospital and were diagnosed with COVID-19 between March 11, 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 scientific committee was established in our hospital to determine a management algorithm for the detection and treatment of pediatric COVID-19 patients. Based on this algorithm, the patients were classified as outpatients or inpatients. All the children admitted to our emergency department with fever, cough, or breathing difficulties were initially evaluated in our COVID-19 examination rooms and then a detailed examination consisting of contact history, underlying comorbidities, physical examination, and laboratory and radiographic workup was performed. A suspected case was defined as an individual presenting with the symptoms of COVID-19 and/or a contact history with an individual diagnosed with COVID-19. As per our hospital protocol, more than 3 month children; a diagnostic lumbar puncture is performed at the time of admission in all patients presenting with ≥2/4 of the classic clinical features of meningitis including headache, fever, meningismus, and altered mental status, less than 3 month children; not sucking , hypoactivity, lethargy, apnea, seizure, fontanel bloating, vomiting, respiratory distress and body temperature changes restlessness, irritability, fever or late sepsis. Patients with focal neurological deficits do not undergo lumbar puncture due to the likelihood of space-occupying lesions and the risk of herniation after lumbar puncture and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 thus CT is performed in such patients. Cerebrospinal fluid (CSF) is sent to the laboratory for standard investigations including Gram stain, India ink stain, bacterial culture, and cryptococcal antigen. Pleocytosis of CSF was defined as a CSF a white blood cell count (WBC) of over 5 cells/μL or neonatal term patients 20 cells/μL. CSF protein levels of >45 mg/dL, neonatal term patients 100 mg/dL were considered abnormal. CSF glucose levels of <40 mg/dL, neonatal term patients 30 mg/dL were considered low. Suspected cases with no positive RT-PCR results were excluded from the study. In this retrospective and non-invasive study, no experiments were conducted on the participants. The study was registered in the database of our medical center (identifier: 2021/53) and an approval was obtained from the local ethics committee. A written informed consent was obtained from each patient. Data were evaluated using SPSS for Windows version 23.0 (Armonk, NY: IBM Corp.). Descriptives were expressed as median and minimum-maximum for continuous variables and as frequencies (n) for categorical variables. Categorical variables were compared using Chisquare test or Fisher's Exact test. Multiple comparisons were performed using Kruskal-Wallis test. A two-tailed p value of <0.05 was considered significant. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 neonate was diagnosed with meningoencephalitis. No neurological symptoms were detected in other patients. Out Patient Departments patients included headache, dizziness, anosmia/dysgeusia, and ageusia/dysgeusia. Neurological complications of OPD patients were detected in 225 (58.9%) patients. Of these, headache was the most common presenting symptom (23%) and the rate of hospitalization due to headache was 38.2%. All the patients with headache were adolescents, who had a mean age of 14.2±3.6 (range, [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] years. In severely symptomatic children who received inpatient care, cranial MRI findings were normal and the longest hospitalization period was 5 days. These patients benefited from hydration and antipyretic and analgesic treatment. The second most common nonspecific symptom was dizziness (14.3%), followed by anosmia (10.2%), and ageusia/dysgeusia (7.3%). No patient was hospitalized due to anosmia and ageusia/dysgeusia. Dizziness was observed in 14.3% of the patients, and 0.7% of them were hospitalized. The patients hospitalized due to dizziness showed a good response to diphenylhydantoin and hydration therapy. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 discharged with full recovery after a meningoencephalitis treatment. No sequela occurred in any patient. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 5% of the patients (25) . Despite these varying rates, in our study, we found a lower frequency of anosmia/ageusia (17.5%) among OPD patients. The frequency of dizziness has been less studied in children. According to the CDC COVID-19 Response Team study, 23% of pediatric patients required follow-up due to dizziness (15) . In our study, dizziness and hospitalization of dizziness were detected in 14.3% and 8.8% of our patients. Febrile seizure is the most common seizure in childhood and is defined as seizures occurring in children aged older than 6 month associated with a febrile disease not caused by an infection of CNS, without previous neonatal seizures or a previous unprovoked seizure, and not meeting the criteria for other acute symptomatic seizures and its incidence varies between 2-5% (28-30). Even so, these children are at risk of developing seizures and encephalopathy, particularly those suffering from severe disease (13) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 As recommended by pediatric associations, it is essential to include the SARS-CoV-2 PCR test in the workup of infants aged less than 3 months (47) . In neonatal children, SARS-CoV-2 test positivity is remarkably low and the most common presenting symptoms include seizure, hypotonicity, and encephalopathy (32,48- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Coronavirus disease 2019 (COVID-19) in children-what we know so far and what we do not Multisystem inflammatory syndrome in children (MIS-C) with COVID-19: insights from simultaneous familial Kawasaki Disease cases COVID-19 associated Multisystem Inflammatory Syndrome in Children (MIS-C) guidelines; a Western New York approach Encephalitis associated with COVID-19 infection in an 11-year-old child Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study Neurological manifestations and complications of COVID-19: a literature review Neurological manifestations of COVID-19 and other coronavirus infections: a systematic review A review of neurological complications of COVID-19 Neurological manifestations of COVID-19: a systematic review and current update Clinical manifestations of children with COVID-19: a systematic review COVID-19 in 7780 pediatric patients: a systematic review Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 Neurogical Complications of SARS-CoV-2 Infection in Children : A Systematic Review and Meta-Analysis Children with COVID-19 in pediatric emergency departments in Italy CDC COVID-19 Response Team. 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COVID-19: Fever syndrome and neurological symptoms in a neonate Neonatal Early-Onset Infection With SARS-CoV-2 in a Newborn Presenting With Encephalitic Symptoms Neurologic manifestations in an infant with COVID-19 The authors are grateful to the personnel of Pediatric Neurology and Policlinic, Pediatric